Erythropoietin receptor

Function

Receptor for erythropoietin, which mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade (By similarity). In some cell types, can also activate STAT1 and STAT3. May also activate the LYN tyrosine kinase (By similarity).

Classification

Family (Pfam)

PF09067 EpoR_lig-bind, PF00041 fn3

InterPro

Erythropoietin_rcpt, FN3_dom, FN3_sf, Growth/epo_recpt_lig-bind, Ig-like_fold, Long_hematopoietin_rcpt_CS

Functional cluster

Secreted Growth Factors & Cytokines

Experimental structures · PDB · 22

• 1CN4 X-ray 2.80A
• 1EBA X-ray 2.70A
• 1EBP X-ray 2.80A
• 1EER X-ray 1.90A
• 1ERN X-ray 2.40A
• 2JIX X-ray 3.20A
• 2MV6 NMR
• 4Y5V X-ray 2.60A
• 4Y5X X-ray 3.15A
• 4Y5Y X-ray 2.85A
• 6E2Q X-ray 2.65A
• 6I4X X-ray 2.69A
• … and 10 more

A predicted model is available from AlphaFold.

Gene Ontology · 7

• GO:0009897 external side of plasma membrane
• GO:0005576 extracellular region
• GO:0005886 plasma membrane
• GO:0004900 erythropoietin receptor activity
• GO:0042802 identical protein binding
• GO:0038162 erythropoietin-mediated signaling pathway
• GO:0007165 signal transduction

Disease associations

• primary familial polycythemia due to EPO receptor mutation MONDO:0007572

Drugs targeting this protein · 1

• CIBINETIDE agonist

Related proteins · sequence + function similarity

• Erythropoietin receptor 0.99
• Erythropoietin receptor 0.99
• Erythropoietin receptor 0.98
• Erythropoietin receptor 0.98
• Interleukin-21 receptor 0.90
• Interleukin-21 receptor 0.90
• Interleukin-2 receptor subunit beta 0.88
• Interleukin-2 receptor subunit beta 0.88
• Interleukin-2 receptor subunit beta 0.88
• Cytokine receptor-like factor 2 0.88
• Interferon upsilon receptor 1 0.87
• Cytokine receptor common subunit beta 0.87

Co-cited proteins · studied together in the literature

• Erythropoietin 1 shared papers
• Suppressor of cytokine signaling 2 2 shared papers
• Suppressor of cytokine signaling 3 1 shared papers
• Regulator of hemoglobinization and erythroid cell expansion protein 1 shared papers
• Ataxin-2-like protein 1 shared papers
• Thrombopoietin receptor 1 shared papers
• SH2B adapter protein 2 1 shared papers
• Growth hormone receptor 1 shared papers
• E3 ubiquitin-protein ligase CBL 1 shared papers
• Tyrosine-protein kinase JAK2 1 shared papers
• Growth factor receptor-bound protein 2 1 shared papers
• Elongin-B 1 shared papers

Literature · 30 cited papers

• Structural insights into substrate recognition by the SOCS2 E3 ubiquitin ligase. Nat. Commun. · 2019
• Analysis of protein-coding genetic variation in 60,706 humans. Nature · 2016
• RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development. J. Exp. Med. · 2014
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Erythropoietin receptors associate with a ubiquitin ligase, p33RUL, and require its activity for erythropoietin-induced proliferation. J. Biol. Chem. · 2003
• A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor. Eur. J. Biochem. · 2002
• Cloning and characterization of a family of proteins associated with Mpl. J. Biol. Chem. · 2002
• Design and application of a cytokine-receptor-based interaction trap. Nat. Cell Biol. · 2001
• Identification of the human erythropoietin receptor region required for Stat1 and Stat3 activation. Blood · 2002
• Increased cell surface expression of C-terminal truncated erythropoietin receptors in polycythemia. Eur. J. Haematol. · 2001
• Engineering a soluble extracellular erythropoietin receptor (EPObp) in Pichia pastoris to eliminate microheterogeneity, and its complex with erythropoietin. Protein Eng. · 1999
• … and 18 more in the literature graph